Synthesis and biological screening of a combinatorial library of β-chlorovinyl chalcones as anticancer,anti-inflammatory and antimicrobial agents

A combinatorial library of β-chlorovinyl chalcones (4) were synthesized by Claisen–Schmidt condensation reaction. Catalytic reaction of substituted 3-chloro-3-phenyl-propenal (2) and 1-(2,4-dimethoxy-phenyl)-ethanone or 1-(4-methoxy-phenyl)-ethanone (3) in alkaline conditions furnished the target compound 5-chloro-1-(2,4-dimethoxy-phenyl)-5-phenyl-penta-2,4-dien-1-one (4). The synthesized compounds were screened for their biological activity viz. anticancer, anti-inflammatory and antimicrobial activities. Synthesized compounds 4g and 4h revealed promising anti-inflammatory activity (66–67% TNF-α and 95–97% IL-6 inhibitory activity at 10 μM). Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Furthermore, the anticancer activity (30–40%) was shown by compounds 4d, 4e, 4h and 4b at 10 μM concentrations against ACHN followed by Calu 1, Panc1, HCT116 and H460 cell lines. Some of the compounds 4d, 4e, 4a, 4i and 4b revealed promising antimicrobial activity at MIC 50–100 μg/mL against selected pathogenic bacteria and fungi.     

Environmental Quality Assessment of Bizerte Lagoon (Tunisia) Using Living Foraminifera Assemblages and a Multiproxy Approach

This study investigated the environmental quality of the Bizerte Lagoon (Tunisia) through an integrated approach that combined environmental, biogeochemical, and living benthic foraminiferal analyses. Specifically, we analyzed the physicochemical parameters of the water and sediment. The textural, mineralogical, and geochemical characteristics of the sediment, including total organic carbon, total nitrogen, simultaneously extracted metals (SEM), acid volatile sulfides (AVS), chlorophyll a, CaCO₃, and changes in bacterial populations and carbon isotopes were measured. The SEM/AVS values indicated the presence of relatively high concentrations of toxic metals in only some areas. Foraminiferal assemblages were dominated by species such as A. parkinsoniana (20–91%), Bolivina striatula (<40%), Hopkinsina atlantica (<17%), and Bolivina ordinaria (<15%) that cannot be considered typical of impacted coastal lagoons both in Mediterranean and northeast Atlantic regions. The results of this work suggest that Bizerte Lagoon is a unique setting. This lagoon is populated by typical marine species that invaded this ecosystem, attracted not only by the prevailing favorable environmental conditions but also by the abundance and quality of food. The results indicate that the metal pollution found in some areas have a negative impact on the assemblages of foraminifera. At present, however, this negative impact is not highly alarming.     

Development of Novel Docetaxel Phospholipid Nanoparticles for Intravenous Administration: Quality by Design Approach

The objective of this study was to develop novel docetaxel phospholipid nanoparticles (NDPNs) for intravenous administration. Modified solvent diffusion-evaporation method was adopted in the NDPN preparation. Central composite design (CCD) was employed in the optimization of the critical formulation factor (drug content) and process variable (stirring rate) to obtain NDPNs with 215.53 ± 1.9-nm particle size, 0.329 ± 0.02 polydispersity index (PDI), and 75.41 ± 4.81% entrapment efficiency. The morphological examination by transmission electron microscopy revealed spherical structure composed of a drug core stabilized within the phospholipid shell. Enhanced cell uptake of coumarin-6-loaded phospholipid nanoparticles by MCF-7 cell line indicated NDPN-efficient cell uptake. In vitro hemolysis test confirmed the safety of the phospholipid nanoparticles. NDPNs exhibited increased area under the curve (AUC) and mean residence time (MRT) by 3.0- and 3.3-fold, respectively, in comparison with the existing docetaxel parenteral formulation (Taxotere®), indicating a potential for sustained action. Thus, the novel NDPNs exhibit an ability to be an intravenous docetaxel formulation with enhanced uptake, decreased toxicity, and prolonged activity.KEY WORDS: cancer, delivery vehicle, docetaxel phospholipid nanoparticles, nanoparticles, pharmacokinetics     

Comparative Phylogenomics and Evolution of the Brucellae Reveal a Path to Virulence

Brucella species include important zoonotic pathogens that have a substantial impact on both agriculture and human health throughout the world. Brucellae are thought of as “stealth pathogens” that escape recognition by the host innate immune response, modulate the acquired immune response, and evade intracellular destruction. We analyzed the genome sequences of members of the family Brucellaceae to assess its evolutionary history from likely free-living soil-based progenitors into highly successful intracellular pathogens. Phylogenetic analysis split the genus into two groups: recently identified and early-dividing “atypical” strains and a highly conserved “classical” core clade containing the major pathogenic species. Lateral gene transfer events brought unique genomic regions into Brucella that differentiated them from Ochrobactrum and allowed the stepwise acquisition of virulence factors that include a type IV secretion system, a perosamine-based O antigen, and systems for sequestering metal ions that are absent in progenitors. Subsequent radiation within the core Brucella resulted in lineages that appear to have evolved within their preferred mammalian hosts, restricting their virulence to become stealth pathogens capable of causing long-term chronic infections.     

Complete sequence and organisation of the <Emphasis Type="Italic">Jatropha curcas</Emphasis> (Euphorbiaceae) chloroplast genome

Jatropha curcas is an important non-edible oil seed tree species and is considered a promising source of biodiesel. The complete nucleotide sequence of J. curcas chloroplast genome (cpDNA) was determined by pyrosequencing and gaps filled by Sanger sequencing. The cpDNA is a circular molecule of 163,856 bp in length and codes for 110 distinct genes (78 protein coding, four rRNA and 28 distinct tRNA). Genome organisation and arrangement are similar to the reported angiosperm chloroplast genome. However, in Jatropha, the infA and the rps16 genes are non-functional. The inverted repeat (IR) boundary is within the rpl2 gene, and the 13 nucleotides at the ends of the two duplicate genes are different. Repeat analysis suggests the presence of 72 repeat regions (>30 bp) apart from the IR; of these, 48 were direct and 24 were palindromic repeats. Phylogenetic analysis of 81 protein coding chloroplast genes from 65 taxa by maximum parsimony, maximum likelihood and minimum evolution analyses at 100 bootstraps provide strong support for the placement of inaperturate crotonoids of which Jatropha is a member as sister to articulated crotonoids of which Manihot is a member.     

Inhibition of angiogenesis- and inflammation-inducing factors in human colon cancer cells <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in ovo</Emphasis> by free and nanoparticle-encapsulated redox dye,DCPIP

Background  

The redox dye, DCPIP, has recently shown to exhibit anti-melanoma activity in vitro and in vivo. On the other hand, there is increasing evidence that synthetic nanoparticles can serve as highly efficient carriers of drugs and vaccines for treatment of various diseases. These nanoparticles have shown to serve as potent tools that can increase the bioavailability of the drug/vaccine by facilitating absorption or conferring sustained and improved release. Here, we describe results on the effects of free- and nanoparticle-enclosed DCPIP as anti-angiogenesis and anti-inflammation agents in a human colon cancer HCT116 cell line in vitro, and in induced angiogenesis in ovo.     

Taxonomic importance of seed macro‐ and micro‐morphology in Abelmoschus (Malvaceae)

Seed morphology of Abelmoschus is known to be variable, but patterns of variation have never been critically studied. We studied seed macro‐ and micro‐morphological characters, including seed shape/size, seed coat pattern and trichome density/structure in multiple samples to evaluate the taxonomic significance of seed characters. Among the studied characters, seed shape and trichome structure were found to have major taxonomic importance and proved to be valuable characters for separating taxa. Two main seed types were present: seeds with deciduous trichomes and seeds with persistent trichomes. These characters offer significant evidence to the distinctness of certain species (A. esculentus, A. moschatus subsp. moschatus, A. moschatus subsp. tuberosus, A. crinitus and A. angulosus). Further, our results indicate that A. moschatus subsp. tuberosus should be maintained as a separate subspecies while A. manihot subsp. tetraphyllus var. pungens may be merged in A. angulosus. No significant intraspecific variation was observed, except in A. esculentus. We conclude that seed coat sculpturing and seed trichomes do indeed provide stable and diagnostic characters for many morphologically closely related taxa of Abelmoschus and that LM/SEM techniques can be useful in solving systematic problems and management of Abelmoschus genetic resources.